Lipid Peroxidation Analytical Core

核心C项目总结 该计划项目的总体目标是测试高密度脂蛋白(Hdl)变化的贡献。 在人类疾病中的作用，特别是动脉粥样硬化。被检验的主要假设之一是，脂质 在各种情况下发生的过氧化反应，会增加动脉粥样硬化的风险(例如，家族性 高胆固醇血症和慢性肾脏疾病)导致高密度脂蛋白被反应性脂质修饰 这些修饰显著改变了高密度脂蛋白的功能。这个核心将提供合成版本 向项目研究人员提供这些反应性二羰基，以便他们可以测试高密度脂蛋白修饰的效果。这 CORE还将提供作为二酮基清除剂的合成化合物，这些化合物可以用于 在动物和人类中培养的细胞，以阻止二碳键与蛋白质和 磷脂酰乙醇胺。这些清道夫既可以用来测试这些二羰基的贡献，也可以用来测试 作为潜在的药物制剂。最后，这个核心将测量蛋白质上的二羰基加合物和 磷脂酰乙醇胺。 目的1：合成IsoLG等二羰基化合物，用于培养细胞和动物模型的实验。 目的2：合成二羰基清除剂，用于培养细胞和动物模型的实验。 目的3：测量二羰基修饰的蛋白质和磷脂酰乙醇胺的量 在动物模型和人类疾病模型中的组织样本和液体中形成。

CORE C PROJECT SUMMARY The overall goal of this program project is to test the contribution of changes in high density lipoprotein (HDL) function in human disease, specifically atherosclerosis. One of the major hypotheses tested is that the lipid peroxidation that occurs during various condition that increase the risk for atherosclerosis (e.g. familial hypercholesterolemia and chronic kidney disease) causes HDL to become modified by reactive lipid dicarbonyls and that these modifications markedly alter HDL function. This core will provide synthetic versions of these reactive dicarbonyls to project investigators so that they can test the effects of HDL modification. This core will also provide synthetic compounds that act as dicarbonyl scavengers and that can be used in both cultured cells, in animals, and in humans to block the reaction of dicarbonys with proteins and phosphatidylethanolamine. These scavengers are useful both to test the contribution of these dicarbonyls and as potential medicinal agents. Finally, this core will measure dicarbonyl adducts on proteins and phosphatidylethanolamine. Aim 1: Synthesize IsoLG and other dicarbonyls for testing in cultured cell and animal models. Aim 2: Synthesize dicarbonyl scavengers for testing in cultured cell and animal models. Aim 3: Measure the amounts of dicarbonyl modified proteins and phosphatidylethanolamines that are formed in tissue samples and fluids in animal models and humans with disease.